The overall goal of the proposed project is to investigate the functional significance of profilin-1 (Pfn1 - a cytoskeleton regulatory protein) downregulation in breast cancer. We will study how Pfn1, a traditionally pro- migratory molecule, can also regulate intracellular signaling generated at the membrane-cytosol interface to suppress breast cancer invasion and metastasis. In Aim 1, we will first combine clinical correlation and mouse model studies to determine whether a) there is a casual relationship between Pfn1 dysregulation and metastatic progression of breast cancer, and b) Pfn1 expression reflects stages in tumor progression and predicts clinical outcome of breast cancer patients (Aim 1). In Aims 2 and 3, we will identify the molecular pathways by which Pfn1 inhibits breast cancer dissemination Successful completion of these studies will determine whether Pfn1 could be used as a prognostic marker in breast cancer and justify novel cancer therapeutics revolving around Pfn1. PUBLIC HEALTH RELEVANCE: Breast cancer ranks second among cancer deaths in women in the United States. In this project, we examine a novel mechanism of how profilin-1, a traditional pro-migratory cytoskeletal protein, regulates signaling at the membrane-cytosol interface and suppresses breast cancer invasion and metastasis. A successful completion of this study will yield novel insights into fundamental tumor cell biology and provide molecular underpinnings of basic adenocarcinoma behaviors that lead to progression.